cholecalciferol and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Current treatment protocols in acute lymphoblastic leukemia (ALL) are associated with high remission rates and long life expectancy, enhancing the importance of quality of life and prevention of treatment-related complications in patient care. As osteoporosis is a frequent complication in patients under chemotherapy, we investigated the effect of vitamin K2 (100 mcg menaquinone-7) and vitamin D3 (10 mcg calcitriol) on bone metabolism in children with ALL.. Twenty-nine consecutive patients recently diagnosed with B precursor ALL (B-ALL) and treated according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Münster 2000 protocol were randomly assigned into study and control groups. The study group (n=15, M/F: 8/7, age 1-14.5 years, mean 6.5 years) received vitamin K2 and vitamin D3 with their chemotherapy, while the control group (n=14, M/F 9/5, age 2-17 years, mean 7.1 years) received chemotherapy only. Serum calcium, phosphorus, magnesium, alkaline phosphatase, bone-specific alkaline phosphatase, uncarboxylated osteocalcin (ucOC), tartrate resistant acid phosphatase 5b, carboxyl terminal procollagen propeptide (PICP), osteoprotegerin (OPG), and receptor activator nuclear kappa B ligand (RANKL) were measured and bone mineral density (BMD) was determined at baseline and first, second, third and sixth months.. The study group had higher serum OPG/RANKL ratio and lower ucOC levels compared to the control group at the first month; PICP levels were higher in the study group at second and third months.. These results suggest an early beneficial effect of the combination of vitamin K2 and vitamin D3 on BMD in ALL patients especially during the period of intensive steroid therapy in the first months.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Bone Density; Child; Child, Preschool; Cholecalciferol; Female; Gene Expression Regulation; Humans; Infant; Male; Osteoporosis; Osteoprotegerin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Procollagen; Prospective Studies; RANK Ligand; Vitamin K 2; Vitamins

Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

Topics: Adolescent; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vitamin D Deficiency

We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation.. This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes.. Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78).. Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry).

Topics: Adolescent; Adult; Bone Density; Calcium, Dietary; Child; Child, Preschool; Cholecalciferol; Counseling; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Lumbar Vertebrae; Male; Nutrition Therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Tomography, X-Ray Computed; Young Adult

The innate immune system produces a number of effector molecules that are important for protection against bacterial infections. Neutrophils and antimicrobial peptides are major components of innate defense with the capacity of rapid bacterial killing. Patients with severe congenital neutropenia (SCN) experience recurrent and chronic infections despite recombinant G-CSF-mobilized neutrophils. We have shown previously that these neutrophils are deficient in that they lack the antimicrobial peptide LL-37. Here, we show that pro-LL-37 mRNA is not expressed in neutrophil precursors from patients with SCN, although the gene and promoter region for pro-LL-37, CAMP, does not display any mutations. The hormonal form of vitamin D3 [1,25(OH)2D3] induced the expression of pro-LL-37 in isolated neutrophil progenitors and in EBV-transformed B cells from patients with SCN, whereas all-trans retinoic acid only induced expression in transformed B cells. These results demonstrate that myeloid cells of patients with SCN can produce pro-LL-37, suggesting that other pathways are impaired.

Topics: Antimicrobial Cationic Peptides; Calcitriol; Cathelicidins; Cell Differentiation; Child; Cholecalciferol; Humans; Neutropenia; Neutrophils; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Siblings; Transcription, Genetic; Tretinoin

Research to detect new factors contributing to the etiology of acute leukemia (AL) is urgently needed. Located between latitudes 65 degrees and 70 degrees north, the population in northern Finland is exposed to extreme seasonal alterations of ultraviolet-B light and temperature. There is also a seasonal variation of both the 25(OH)- and 1,25(OH)2-D3 vitamin serum concentrations. In the present work, the frequencies of different types and age-groups at diagnosis of AL were compared during the dark and light months of the year, to uncover seasonality. Between January 1972 and December 1986, 300 consecutive patients aged >/=16 years and diagnosed as having AL were enrolled. The observed mean monthly global solar radiation, temperature measurements, and influenza epidemics were compared with the monthly occurrence of AL. Both acute lymphoblastic leukemia (ALL) (p=0.006) and total AL (p=0.015) were diagnosed excessively in the dark and cold compared with light and warm period of the year. There was a tendency for de novo leukemia to increase also in the dark and cold, but for acute myeloid leukemia (AML) patients the excess was not significant. Age >/=65 was strongly associated with the dark and cold season (p=0.003). Significantly more ALL (p=0.005) and de novo leukemias (p=0.029) were observed during influenza epidemics than during nonepidemic periods. However, a seasonality, i. e., the fluctuation of numbers of AL cases, was not determined, either monthly or during different photo- and temperature periods or influenza epidemics; this might be due to the small numbers of patients studied. Nevertheless, it is hypothesized that sunlight deprivation in the arctic winter can lead to a deficiency of the 1, 25(OH)2D3 vitamin, which might stimulate leukemic cell proliferation and block cell differentiation through dysregulation of growth factors in the bone marrow stromal cells, causing one mutation and an overt ALL in progenitor cells damaged during the current or the previous winter by influenza virus, the other mutation.

Topics: Acute Disease; Adolescent; Adult; Aged; Cholecalciferol; Cold Temperature; Disease Outbreaks; Female; Finland; Humans; Influenza, Human; Leukemia; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Seasons; Ultraviolet Rays